The remarkable transport mechanism of P-glycoprotein: A multidrug transporter

Human P-glycoprotein (ABCB1) is a primary multidrug transporter located in plasma membranes, that utilizes the energy of ATP hydrolysis to PUMP toxic xenobiotics out of cells. P-glycoprotein employs a Most unusual molecular mechanism to perform this drug transport function. Here we review Our work to elucidate the molecular mechanism of drug transport by P-glycoprotein. High level heterologous expression of human P-glycoprotein. in the yeast Saccharomyces cerevisiae, has facilitated biophysical Studies in Purified proteoliposome preparations. Development of novel spin-labeled transport substrates has allowed for quantitative and rigorous measurements of drug transport in real time by EPR spectroscopy. We have developed a new drug transport model of P-glycoprotein from the results Of mutagenic, quantitative thermodynamic and kinetic studies. This model satisfactorily accounts for most of the unusual kinetic, coupling, and physiological features of P-glycoprotein. Additionally, an atomic detail structural model of P-glycoprotein has been devised 10 place Our results within a proper structural context.